Primary cilia are now believed to be present in all mammalian cell types and act as environmental sensors. Generally, these cilia exhibit relatively simple structures. However, sensory cell types such as the kinocilia in the ear and olfactory sensory cilia exhibit highly specialized cilia structures that are essential for their specialized sensory functions. Although much is now known about how primary cilia are formed, very little is understood about the processes of building and maintaining specialized cilia. Loss of kinocilia or olfactory cilia function result in hearing loss and anosmia. Thus, understanding how these specialized cilia form and function is essential for a complete understanding of how animals smell and hear. C. elegans is an excellent model system in which to study the mechanisms of specialized cilia formation. Several chemosensory neuron types in C. elegans exhibit highly specialized cilia, which are essential for their sensory functions. The goal of this research is to define the genetic mechanisms required for the generation of specialized chemosensory cilia types. Using a proteomics-based approach, an unconventional myosin HUM-4 was identified as a candidate ciliary molecule. Mutations in hum-4 lead to ciliary defects specifically in an olfactory neuron type. Unconventional myosins have previously been implicated in maintenance of both kinocilia and stereocilia structures in the inner ear, and are mutated in hearing disorder syndromes such as Usher syndrome. The goal of this proposal is to investigate the functions of HUM-4 in the generation of specialized olfactory cilia morphology in the C. elegans model system. These cilia structures are essential for neuron-specific chemosensory responses so how sensory neurons are specialized for their unique functions will also be described. The proposed specific aims are: 1. Characterization of the role of the HUM-4 unconventional myosin in the regulation of ciliary morphology. 2. Elucidation of the mechanism by which the HUM-4 unconventional myosin regulates AWB ciliary morphology. PUBLIC HEALTH RELEVANCE: A thorough understanding of these mechanisms is important for a complete understanding of how humans hear and smell. This work will lead to a better understanding of how specialized cilia are formed, and how defects in cilia structure lead to sensory dysfunction.